The mammalian fetus in an outbred population invariably expresses antigens, some of them histocompatability antigens which are derived from both parents. If those antigens were expressed by allografts of other tissue, the grafts would be rejected, yet the fetus develops with few complications within the uterine environment. Obviously this is an immunologic enigma. A general theory has evolved which suggests that one reason for survival of the fetal allograft is the development of local immunoregulation. The rationale for the present proposal is that tissues surrounding the fetus, the uterus, placenta and yolk sac, contain suppressor cells which prevent rejection of fetal tissue. The research described herein is designed to localize, identify and quantify immunologic cells (lymphocytes, macrophages and granulocytes) within tissue that surrounds the fetus, i.e., the uterus, placenta and yolk sac. It is then designed to determine the degree of suppressor cell activity for T-lymphocyte mediated cell function, determine the nature of the suppressor cells and begin to understand by what mechanism the suppressor cells act to modulate lymphocyte function. Finally experiments will be performed to evaluate the effect on pregnancy of agents which block the activity of the putative suppressor cells. These series of experiments should allow us to determine 1) if immunoregulation occurs and is important in promoting fetal survival and 2) what cells are responsible for immunoregulation.